1. Technical Field
The present invention relates to methods of treating cancer. More specifically, the present invention relates to the use of an immunomodulating agent for the treatment of cancer.
2. Background Art
There are a number of therapies that are currently used in the treatment of cancer, including chemotherapeutic drugs, radiation, gene therapy, and antisense oligonucleotides. One drawback to these current therapies is the toxicity associated with most treatments, especially when such therapeutics are combined. Moreover, often large dosages must be administered over an extended period of time in order to attain therapeutic benefit. Thus, a need remains for more effective treatments that reduce the risk of toxicity and can be used in lower doses.
VIRULIZIN® (Lorus Therapeutics) is an immunotherapeutic agent that stimulates a patient's immune system to produce anti-tumor effects through several mechanisms, including the activation of macrophages including increasing TNF-α release and increasing production and secretion of IL-17E by B cells resulting in expansion in number of and increased infiltration of eosinophils and natural killer (NK) cells into tumors. The production and characterization of this bile-derived immunotherapeutic agent has been described in International Patent Application Serial No. PCT/CA94/00494, published Feb. 16, 1995 as WO 95/07089, International Patent Application Serial No. PCT/CA96/00152, published Sep. 19, 1996 as WO 96/28175, and U.S. Pat. No. 6,280,774. The use of VIRULIZIN® as an anti-viral has been described in International Patent Application Serial No. PCT/CA98/00494, published Nov. 26, 1998 as WO 98/52585.
VIRULIZIN® is comprised of small molecular weight components of less than 3000 daltons, and has one or more of the following properties: (i) is extracted from bile of animals; (ii) is capable of stimulating natural killer (NK) cells, eosinophils, monocytes and/or macrophages in vitro and/or in vivo; (iii) is capable of modulating tumor necrosis factor production and/or release; (iv) contains no measurable level of IL-1α, IL-1β, TNF, L-6, TL-8, IL-4, GM-CSF or IFN-γ; (v) shows no cytotoxicity to human peripheral blood mononuclear cells or lymphocytes; (vi) is not an endotoxin, and (vii) Inhibits growth of a variety of human tumor xenograft models in mice including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer.
Cancer clinical studies generally use performance status score as enrollment criteria, especially ECOG scale (or other methods of investigator determination of patient score, e.g. Karnofsky, WHO, Zubrod, or Lansky Scale for children). ECOG scores of either 0 and 1 or 0, 1, and 2 are generally used as selection criteria at the time of study enrollment to select patients who are capable of self-care with minimal assistance and have an higher probability of a duration of survival to allow sufficient study treatment to evaluate the safety and efficacy of the cancer treatment. No randomized placebo controlled cancer trial testing a combination of therapeutics, other than the present study has reported a highly statistically significant (p<0.001) increase in median survival observed only for the population of patients of ECOG score of 0 or 1 where the survival response (versus placebo) is specific to the treatment group receiving the test agent and there is not also at least modest increased survival versus placebo for the test agent treatment group in the ECOG score of 2 (or greater) patient population
It is unexpected that only within the patient population with study enrollment ECOG score of 0 or 1 there is a highly statistically significant increase in median survival comparing the salvage treatment group treated with VIRULIZIN® (or any study drug) plus 5-FU or other chemotherapeutic and the treatment group treated with placebo plus 5-FU or other chemotherapeutic. It would be advantageous to be able to combine VIRULIZIN® with other cancer treatments in order to make these treatments more effective as well as reduce their toxicity. Furthermore, it would be advantageous to determine if VIRULIZIN is more effective for certain sets of patients than others to provide better treatment.